Genetic testing for drug intolerance makes sense

Testing could prove an effective remedy to the widespread problem of adverse drug reactions. However, there are cost concerns — and hidden hazards to our privacy

By Angela Saini / The Guardian, LONDON

Illustration: Mountain People

Three years ago, Theo Dingermann, a professor of pharmaceutical biology at Goethe University in Frankfurt, sent a glob of spit to the US. For US$200 a company there sequenced part of his genome using DNA from his cheek cells. The test revealed that if he were to take the cholesterol-lowering drugs statins, they would have little effect. In fact, they might harm him.

“I’m healthy at the moment, but if I took statins, there’s a risk I would get muscle pain,” he says.

Statins work through the blood, coursing through the body until they reach the liver. Here, they pass through a door, known as a carrier, which takes them from the blood into the liver, where they lower cholesterol production. Dingermann’s genetic test showed that he has fewer carriers than usual, which means that statins could stay in his bloodstream and start harmfully reducing the cholesterol in his muscles instead.

Realizing that he might have to live without these artificial cholesterol-busters, he decided to get healthy.

“I lost some kilos and started running. Last year, I jogged 1,400km,” he said.

Intolerance to a drug is something most people learn about themselves only after it is prescribed.

“There are some tumor drugs, for certain cancers, that 70 percent of the population won’t respond to. For some asthma drugs, it’s 40 percent,” said Dingermann, who has been collecting research on the topic for the past four years.

His source is a 2001 article published in the journal Trends in Molecular Medicine, which also stated that antidepressants were ineffective for 38 percent of people, diabetes drugs for 43 percent, arthritis drugs for 50 percent and Alzheimer’s drugs for as many as 70 percent.

Ann Daly, a professor of pharmacogenetics at Newcastle University Medical School, said these rates are difficult to verify. Some people, for instance, do not take the medicines they are prescribed. However, for a very small minority, the consequences of taking their medications are dire. A paper in the Journal of the American Medical Association in 1998 estimated that adverse drug reactions ranked between the fourth and sixth-biggest killers in the US.

“Medical practice hasn’t changed all that much since this paper appeared. Adverse drug reactions remain a big killer in Europe, as well as in the US,” Daly said.

Part of the problem lies in how medicines are developed. Clinical trials deliberately ignore a patient’s background and genetics so they can avoid bias, but this in turn means that, so long as a drug works well for most people, doctors will prescribe it to everyone with that condition.

“Such a study doesn’t tell you how a particular patient responds to a drug. Some people have a personal biochemistry which means it doesn’t work at all,” Dingermann said.

The tiny risk of side effects is something we accept almost every time we swallow a pill, but Dingermann said it is one we need no longer live with. If everyone had their genomes analyzed the way he did and if medical trials included patients’ genetic backgrounds, they could steer clear of the drugs that do not suit them, he said. He has been urging governments and health insurance companies to adopt widespread genetic testing. This kind of personalized medicine could save millions in unnecessary medical bills.

Scientists are beginning to back the idea with greater force. A report in January by the Human Genomics Strategy Group, which advises the UK government, laid out a vision for the British health service in 2020 that includes using patients’ genetic profiles to avoid drugs that could harm them. The group’s chair, Sir John Bell, a former president of the Academy of Medical Sciences, said that a national DNA database might be needed in the future.